Mechanical ventilation is a treatment that supports and assists breathing in patients with impaired lung function. It is used to treat a wide range of indications, including acute respiratory distress syndrome (ARDS), apnea, asthma, chronic obstructive pulmonary disease (COPD), acute respiratory acidosis, tachypnea, respiratory distress, respiratory support of premature neonates, hypoxemia, cardiogenic and non-cardiogenic pulmonary edema, and drug-induced or neurological impairments of the diaphragm. Mechanical ventilators are available for both acute and non-acute settings (e.g., intensive care, neonatal, portable units for emergency transport and home use, and sleep apnea devices).
Invasive ventilation provides oxygen using an artificial airway, e.g., an endotracheal or tracheostomy tube. Noninvasive ventilation (NIV) provides oxygen through an external interface, e.g., a mouth or nose piece, or a face mask. Ventilators can provide room air and/or supplemental oxygen. The fraction of oxygen in the inspired air (FiO2) can range from 0.21 (21%) as in room air, or up to 1.0 (100%) oxygen in critical cases. Ventilators can also assist breathing by providing positive pressure in a continuous or intermittent fashion (e.g., positive end-expiratory pressure (PEEP) and continuous positive airway pressure (CPAP)).
Because the goal of ventilation is to ensure sufficient oxygenation of the body, various measurements have been used to assess the sufficiency of the intervention. If sufficient oxygenation is achieved, the physician may choose to withdraw or wean the patient from ventilation (e.g., by extubation, or by removing NIV). By contrast, if insufficient oxygenation is detected, the physician may choose to escalate to a more aggressive means of respiratory support (e.g., from NIV to intubation). While initiating mechanical ventilation is often a life-saving intervention, it carries risks and complications, especially with prolonged use, including barotrauma, ventilator-associated lung injury (VALI), diaphragm atrophy, and increased mucus potentially leading to pneumonia. Accordingly, it is desirable to apply mechanical ventilation only for the duration and intensity that is medically necessary.
To measure lung oxygenation and lung injury severity, clinicians have historically relied on the ratio of the partial pressure of oxygen in the arterial blood (PaO2) and the fraction of inspired oxygen (FiO2), i.e., a PaO2/FiO2 ratio, or P/F for short). Arterial blood is the blood that leaves the lungs after oxygenation, and therefore measuring PaO2 requires an invasive arterial blood sample (invasive stick of the artery or catheter) and specialized equipment (blood gas machine). Thus, P/F can only be obtained in skilled facilities with clinical staff (physicians and respiratory therapists). Another limitation is that PaO2 measures oxygen dissolved in blood plasma rather than oxygen saturation of blood hemoglobin (SpO2), which more directly reflects oxygen delivery to body tissues.
FIG. 1 shows an oxygen dissociation curve, which shows the nonlinear relationship between SpO2 and PaO2. This curve depends on the fraction of oxygen gas delivered (FiO2) by a ventilator, or the amount of oxygen delivered in liter-per-minute by air or mask in a portable, standalone system. (For simplicity, all oxygen delivery systems are herein described as delivering oxygen as measured in “FiO2.”). In FIG. 1, normal arterial blood values of SpO2 and PaO2 are shown assuming breathing room air with an FiO2 of 0.21 (21%). If the lungs are damaged, SpO2 will be less than the normal SpO2 range of 95 to 99%. Using oxygen, positive pressure (mechanical) ventilation (e.g. increased tidal volume and respiratory rate) or positive expiratory pressure (PEEP), the caregiver can often increase SpO2 to the within the normal range, but in severely diseased lungs, it may not be possible to reach a normal SpO2 level.
Increasing the fraction of oxygen (FiO2) can drastically increase PaO2, up to hundreds of mmHg. But this has very little added benefit to SpO2, which plateaus around 95%. Thus, when a patient is ventilated, a SpO2 of greater than 95% does not accurately indicate PaO2. In practice, excessive FiO2 is often delivered out of an abundance of caution under the presumption that hypoxemia presents a greater risk that hyperoxemia. See H. Gershengorn, “Hyperoxemia—Too Much of a Good Thing?” Critical Care, 18:556 (2014); R. Branson & B. Robinson, “Oxygen: When is More the Enemy of Good?” Intensive Care Medicine, 37:1-3 (2011).
Similarly to P/F, clinicians have used the SpO2/FiO2 ratio (S/F) to assess oxygenation, and use of S/F has been validated to assess prognosis and severity of acute lung injury. T. Rice et al., “Comparison of the SpO2/FiO2 Ratio and the PaO2/FiO2 Ratio in Patients with Acute Lung Injury or ARDS,” CHEST, 132:410-17 (2014); W. Chen et al., “Clinical Characteristics and Outcomes are Similar in ARDS Diagnosed by Oxygen Saturation/FiO2 Ratio Compared with PaO2/FiO2 Ratio,” CHEST, 148:1477-83 (2015); “Hamilton-G5: Technical Specifications for SW Version 2.6x or Higher,” Hamilton Medical (2016) (downloaded from https://www.hamilton-medical.com/Products/Mechanical-ventilators/HAMILTON-G5.html) (noting that Hamilton-G5 ventilator product includes closed-loop control and optional “numerical monitoring of SpO2/FiO2 ratio as an approximation to PaO2/FiO2 ratio.”). S/F has also been used to identify and/or predict NIV (non-invasive ventilation) failure in adult and pediatric patients, i.e., as an indicator that more aggressive intervention, e.g., intubation, is needed. C. Spada et al., “Oxygen Saturation/Fraction of Inspired Oxygen Ratio is a Simple Predictor of Noninvasive Positive Pressure Ventilation Failure in Critically Ill Patients,” J. Critical Care, 26:510-16 (2011); J. Mayordomo-Colunga et al., “Predicting Non-Invasive Ventilation Failure in Children from the SpO2/FiO2 (SF) ratio,” Intensive Care Med., 39:1095-1103 (2013); U.S. Pat. No. 8,554,298.
Unlike PaO2, SpO2 can be measured noninvasively, for example, by pulse oximetry. Thus, SpO2 can be measured in less specialized settings, and can be measured more frequently, or even continuously, to provide rapid feedback of oxygenation status. Such data could be automatically incorporated into an electronic medical record. And because SpO2 is a measure of blood hemoglobin saturation (rather than plasma oxygen concentration), it is a direct reflection of the oxygen-carrying capacity of the blood. However, only a few commercially available ventilators include an integrated pulse oximeter to measure SpO2. See, e.g., “Hamilton-G5: The Modular High-End Ventilation Solution,” Hamilton Medical (2016) (downloaded from https://www.hamilton-medical.com/Products/Mechanical-ventilators/HAMILTON-G5.html); CareFusion Corp., “ReVel® Ventilator: Taking Portability to New Heights,” (2015) (downloaded from http://www.carefusion.com/Documents/brochures/respiratory-care/mechanical-ventilation/RC_ReVel-Ventilator_BR_EN.pdf); Zoll Medical Corp., 731 Family of Portable Ventilators (2016) (downloaded from https://www.zoll.com/medical-products/ventilators/);
The S/F ratio closely approximates the P/F ratio under many conditions. Accordingly, guidelines from the National Institutes of Health's National Heart, Lung, and Blood Institute (NIH-NHLBI) state that for ARDS treatment, the least amount of oxygen (FiO2) should be used to maintain SpO2 at 88-95%, which is equivalent to a PaO2 of 55-80 mmHg, as shown by the region in FIG. 1 bounded by the dotted lines. See http://www.ardsnet.org/files/ventilator_protocol_2008-07.pdf (downloaded 2016). A SpO2 of 88-95% corresponds to a relatively steep portion of the oxygen dissociation curve of FIG. 1 where PaO2 is also changing significantly. Beyond that range, i.e., increasing PaO2 above 80 mmHg, makes little difference in SpO2. Other literature consistent with these NIH-NHLBI ARDS guidelines also suggests maintaining SpO2 within this range to decrease oxygen consumption. P. Jernigan et al., “Portable Mechanical Ventilation with Closed-Loop Control of Inspired Fraction of Oxygen Maintains Oxygenation in the Setting of Hemorrhage and Lung Injury,” J. of Trauma & Acute Care Surgery, 79(1):53-59 (2015) (suggesting an SpO2 of 94%); S. Satoshi et al., “Conservative Oxygen Therapy in Mechanically Ventilated Patients: A Pilot Before-and-After Trial,” Critical Care Medicine, 42(6):1414-22 (2014) (suggesting an SpO2 of 90-92%).
Despite the above-referenced NIH-NHLBI guidelines to maintain SpO2 at 88-95%, in practice, SpO2 is frequently maintained at very high levels (e.g., greater than 95%, greater than 98%, or even at or nearly 100%). Setting SpO2 above 95% can mask the diagnostic value of S/F and results in several clinical consequences. First, at very high SpO2, the SpO2 and PaO2 become discordant, because higher FiO2 will raise PaO2 with little effect on SpO2. Second, at very high SpO2, it may take several additional minutes to recognize a change in lung function. Finally, in addition to the delay in recognizing a change in lung function, there is also a delay of several minutes to hours for the caregiver to adjust the ventilation settings in response to the change in lung function.
The art has provided Closed Loop Control (CLC) to automatically adjust ventilation parameters (e.g., FiO2, positive pressure, etc.) in response to feedback from the system to maintain oxygenation targets. M. Wysocki et al., “Closed Loop Mechanical Ventilation,” J. Clinical Monitoring & Computing, 28:49-56 (2014); R. Chatburn & E. Mireles-Cabodevila, “Closed-Loop Control of Mechanical Ventilation: Description and Classification of Targeting Schemes,” Respiratory Care, 56(1):85-102 (2011).
Closed Loop Control of FiO2 (CLC-FiO2) automatically adjusts the fraction of inspired oxygen (FiO2) delivered in response to changes in ventilation parameters to maintain target values for SpO2. An example of a system 10 in which this occurs is shown in FIG. 2. System 10 includes an oxygen delivery system 12 that provides an oxygen fraction FiO2 to a patient 14. Oxygen delivery system can comprise both ventilators (e.g., devices equipped to be capable of providing mechanical breathing assistance) and portable “stand alone” oxygen delivery devices that simply provide O2. Such oxygen can be provided to the patient through a mask (e.g., face mask, mouth piece, nose piece, nasal cannula), tube (e.g., an endotracheal or tracheostomy tube), or chamber (e.g., a hyperbaric chamber) 16. The patient wears an oximeter sensor 18, usually on a fingertip, which detects SpO2. This SpO2 reading is reported back to an FiO2 adjust algorithm 20 in the oxygen delivery system 12, which can operate in logic circuitry (e.g., a microprocessor, microcontroller, DPS, FPGA, or similar logic device) in the oxygen delivery system 12. System 10 further includes a display monitor 22, which may be used to provide visual indication of operation of the oxygen delivery system 12 to a clinician. Display monitor 22 may be incorporated within the body of the oxygen delivery system 12 as is common, or may be a self-standing display monitor connected to the oxygen delivery system via a cable. Oxygen delivery system 12 may comprise a mechanical ventilator, a portable mechanical ventilator, or a neonatal mechanical ventilator.
Depending on the SpO2 reading, the FiO2 adjust algorithm 20 can either increase or decrease the oxygen fraction FiO2 to keep SpO2 within a desired range, such as 90-95%. For example, if SpO2 falls, the system can automatically increase the FiO2 delivered to maintain SpO2 within the target range. Conversely, as SpO2 improves, the system 10 can automatically decrease the FiO2 delivered to facilitate weaning from invasive ventilation. FiO2 adjust algorithm 20 can also operate to adjust FiO2 up or down depending on a rate of change of SpO2. See Chatburn & Mireles-Cabodevila, cited above. Furthermore, many Closed Loop systems include will provide 100% FiO2 if SpO2 falls below 88% for a certain amount of time. Tight control of SpO2 by using CLC-FiO2 results in less hypoxia, less hyperoxia, and less FiO2 use. J. Johannigman et al., “Autonomous Control of Inspired Oxygen Concentration During Mechanical Ventilation of the Critically Injured Trauma Patient,” J. TRAUMA Injury, Infection, and Critical Care, 66:386-392 (2009); Wysocki, cited above. Exemplary portable oxygen delivery systems utilizing CLC-FiO2 and integrated pulse oximetry include those described in U.S. Pat. Nos. 9,364,623 and 6,675,798.
Using CLC-FiO2 to maintain a target SpO2 has been used for:                automatic weaning from invasive ventilation for adult and pediatric patients. K. Burns et al., “Automating the Weaning Process with Advanced Closed-Loop Systems,” Intensive Care Med., 34:1757-65 (2008); L. Rose, “Strategies for Weaning from Mechanical Ventilation: A State of the Art Review,” Intensive & Critical Care Nursing, 31:189-195 (2015);        remote medical care in austere environment. Johannigman, cited above;        maintaining oxygenation in lung injury. Jernigan, cited above, (noting that “a portable ventilator modified with a CLC algorithm, which uses feedback from pulse oximetry (SpO2) and FiO2 trends to adjust FiO2 and maintain a target SpO2 of 94%.”); and        automated oxygen supplementation for neonatal intensive care unit (NICU). M. Hutten et al., “Fully Automated Predictive Intelligent Control of Oxygenation (PRICO) in Resuscitation and Ventilation of Preterm Lambs,” Pediatric RESEARCH, 1-7 (2015).        